The Effect of Intratumoral Interrelation among FOXP3+ Regulatory T Cells on Treatment Response and Survival in Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is characterized by an active immune response. We evaluated intratumoral interrelation between FOXP3+ tumor-infiltrating lymphocytes and other cytokines in TNBC. Network analysis refined cytokines significantly correlate with FOPX3 in TNBC. Information on the treatment response and prognosis of patients, and survival data from the TGCA and METABRIC databases were analyzed according to refined cytokines. Interleukin (IL)-33 was significantly expressed by TNBC cell lines compared to luminal cell lines (log2 fold change: 5.31, p < 0.001) and IL-33 and TGFB2 showed a strong correlation with FOXP3 in the TNBC cell line. Immunohistochemistry demonstrated that the IL-33 high group was a significant predictor of complete response of neoadjuvant chemotherapy (odds ratio (OR) 4.12, p < 0.05) and favorable survival compared to the IL-33 low group (OR 6.48, p < 0.05) in TNBC. Survival data from TGCA and METABRIC revealed that FOXP3 was a significantly favorable marker in the IL-33 high group compared to the low IL-33 low group (hazard ratio (HR) 2.1, p = 0.02), and the IL-33 high/TGFB2 high subgroup showed significant favorable prognosis in the FOXP3 high group compared to the FOPX3 low group in TNBC (HR 3.5, p = 0.01). IL-33 and TGFB2 were key cytokines of intratumoral interrelation among FOXP3 in TNBC.